The goal of this grant, from its inception, has been to understand the pathophysiology and time-course of the neurological and cognitive sequelae of CABG. In our previous funding cycles we focused on the early postoperative changes associated with CABG that included: neurological and cognitive effects in the immediate postoperative period, and cognitive performance at 1 month, 3 months and 1 year after surgery. We have found that by 3 and 12 months after surgery, the cognitive performance of CABG patients does not differ from that of a nonsurgical control group with cardiovascular disease. This suggests that cognitive changes during the immediate postoperative period, if present, may be transient and reversible. However, our findings, as well as those of other groups, indicate that there may be additional important longterm cognitive sequelae that occur many years after CABG (i.e., 5 years following surgery)1. In one study, 42% of patients had significant decline at 5 years2. With more than 400,000 having CABG per year, this translates into an incidence of 160,000 patients with potentially preventable cognitive decline. The relationship of these late changes to CABG remains unclear, however, because previous studies have not included appropriate control groups. In this competing continuation, we compare the CABG group with 3 control groups with the goal of defining the long-term outcomes associated with CABG, with the ultimate goal of providing a rationale for interventions to prevent these complications. The four study groups are: 1) Coronary Artery Bypass Grafting (CABG): surgery using cardiopulmonary bypass and aortic cross-clamping 2) Off-Pump Coronary Artery Bypass (OPCAB): Patients with surgery on the beating heart under general anesthesia, but without cardiopulmonary bypass, and with minimal aortic clamping/manipulation 3) Non-surgical controls (NSC): Patients with coronary artery disease, who have not had surgery 4) Healthy Control (HC): Subjects without known cardiovascular or cerebrovascular risk factors. Our overall hypothesis is that late cognitive decline after CABG may be related to underlying cerebrovascular disease, possibly augmented by effects of microemboli during surgery. In the next funding cycle, by comparing the performance of the above groups in several cognitive domains, we will define the nature, time-course and specificity of late changes in cognition associated with CABG, with the following specific aims: Specific Aim 1: To determine if late cognitive change over 5 years is specific to CABG Specific Aim 2: To identify those cognitive domains affected by CABG over a 5-year period. Specific Aim 3: To develop a statistical model that predicts cognitive change in CABG and/or other populations at risk for cerebrovascular disease over the 5-year follow-up period.